The Health Controversies of Parabens

1Department of Dermatology and Skin Science, University of British Columbia, Vancouver, BC, Canada2Division of Dermatology, Department of Medicine, St. Paulís Hospital, Vancouver, BC, Canada.

Introduction

Parabens are preservatives used in a wide range of cosmetic, pharmaceutical and food products. Parabens are esters of parahydroxybenzoic acid and commonly include methylparaben, ethylparaben, propylparaben and butylparaben.1 The recent health concerns regarding parabens stem from a study published in 2004 that detected parabens in breast tissue from patients with breast cancer.2 Public pressure has persuaded several governments to introduce regulations on the use of parabens in consumer products. In this review, we examine the data regarding the health effects of parabens to provide a better understanding of this issue.

One study identified parabens in 44% of cosmetics tested.3 In personal care products tested in the US, concentrations of up to 1.0% methylparaben were found, with lipstick having the highest concentration.1

The other parabens are used at concentrations lower than methylparaben in personal care products.

Methyl and propylparaben are the most commonly used parabens in pharmaceutical products.1

Methyl and propylparaben are also used in food products such as jams, jellies, fillings and toppings.1,5

Parabens in the Human Body

Parabens can enter the human body through the skin, parenterally and intravenously.

The average daily total personal paraben exposure is estimated to be 76 mg, with cosmetics and personal care products accounting for 50 mg, pharmaceuticals for 25 mg, and food for 1 mg.6,7,8

Parbens applied to the skin are metabolized by keratinocyte carboxylesterases and the conjugated metabolites are excreted in urine and bile.9,10

Oral or intravenous parabens are metabolized by esterases within the intestine and liver.1

Parabens have been detected in urine, serum, breast milk and seminal fluid: most worrisome has been the detection in breast tissue from patients with breast cancer.2,11-15

Some have hypothesized that the higher concentration in the upper lateral breast near the axilla correlates with exposure from underarm deodorant and an increased incidence of breast cancer development in the area.16,17 Still, absolute concentrations indicate that levels of parabens within human fluids and tissue are low [average urine concentrations in the US range from 0.5 to 680 ng/mL and breast tissue concentrations range from 0 to 5100 ng/g of breast tissue (the median being 85.5 ng/g)].14,15

These low concentrations should be interpreted in the context of known estrogenic effects of parabens.

Toxicity and Adverse Effects of Parabens

Human and animal studies have failed to show that parabens have any acute toxicity by various routes of administration.

Many studies examining paraben toxicity have focused on the long-term effects of chronic exposure.

The estrogenic activity of parabens was first identified in 1998 and subsequently validated in vitro and in vivo.1,18,19

Parabens bind human estrogen receptors, although with affinities 10,000 to 1,000,000 times less than estradiol.18,20 Butyl and propylparaben have higher estrogenic activity than methyl or ethylparaben but are detected at concentrations 10 to 1000 times less than methylparaben in humans.21

The estrogenic effects in vivo have been demonstrated by uterine growth assays in mice and rats.1,22 However, this effect did not prevent implantation of a fertilized egg, which is considered the most sensitive measure of estrogen toxicity.22,23

It has been hypothesized that the estrogenic activity of parabens may promote breast cancer development.

The concentration of estradiol in normal human breast tissue is 55.3 pg/g, suggesting there is a safety margin of 10 to 1000 times for parabens to approximate normal estradiol activity.1,14,21

Paraben breast cancer data show no or low parabens in a subset of patients and there are no comparisons with normal controls.2,14

With no established correlation, it is difficult to put forth a causal relationship between parabens and breast cancer development.

Another major area of study has been the effect of parabens on the male reproductive system but results are conflicting.24

Men with fertility problems including low sperm count and decreased motility were assayed for paraben exposure by measuring urine paraben levels.12 No correlation between sperm count or motility and parabens levels was found.

Parabens, as is the case for many preservatives, can be allergenic in a small subset of the population, and commonly manifests as an eczematous rash.

The rates of reported sensitization to parabens range from 0.5% to 3.5% and are among the lowest of all preservatives.6,7

Additionally, there are reports of immediate IgE-mediated allergic reactions to parabens resulting in urticaria and, in one case, bronchospasm.25,26 However, these immediate allergic reactions are extremely rare.

Government and Regulatory Control of Parabens

Government regulatory boards have examined parabens and most have agreed that current concentrations of parabens are safe for consumer use.

The European Union (EU) has set up limits on paraben use that have also been reviewed by the European Scientific Committee on Consumer Products (SCCP).

In 2006, the SCCP concluded that parabens can be safely used in cosmetic products at concentrations of 0.4% for any individual paraben and 0.8% for total paraben concentrations.1,27 These limits echo the legislative limits put in place by the EU.

In 2011, the Danish government banned the use of parabens in personal care products intended for children younger than 3 years of age.28

In the US, the Cosmetic Ingredient Review (CIR) has recommended the same maximum paraben concentrations as suggested by the SCCP and as legislated by the EU.1 However, the CIR recommendations are only guidelines which manufacturers are not required to follow.

In Canada, there are no laws regulating paraben concentrations but Health Canada agrees with the US FDA and the CIR regarding the safety of parabens and the adoption of maximum concentration guidelines.29

These "natural" preservatives inhibit microbial growth in vitro but the few studies testing antimicrobial activity in food products have provided equivocal results, and therefore require further study.32,34,35

Conclusion

We have come to expect long shelf-lives and microorganism free consumer products. This mandates the use of preservatives. Ideally, preservatives should be active against a wide variety of microorganisms, at low concentrations, without interfering with other ingredients in the product, while being nontoxic to humans and low cost to manufacturers. Parabens have been used for over 80 years and despite reports of adverse reactions, they have proven to be amongst the safest and most well tolerated preservatives. While the possible role of parabens in decreased sperm quality and breast cancer does warrant continued examination, the current data does not support drastic regulations or personal restrictions to exposure. Other recently regulated chemicals, such as phalates and bisphenol-A, may serve as archetypes for continued vigilance and investigation.36,37